Russel E. Kaufman
Professor Emeritus of Medicine

The overall focus of this laboratory is the study of the genetic regulation of normal and leukemic hematopoietic cells. Hematopoietic stem cells are produced during embryonic and fetal development and migrate to fetal liver, spleen, thymus, and bone marrow to populate those organs for the "definitive" stages of hematopoiesis.

We have cloned and determined the structural organization of the human c-kit gene, normally expressed on erythroid progenitors, and identified important regulatory elements in its promoter. Furthermore, we have identified the ets transcription factors as mediators of its signaling pathway and have isolated a novel ets transcription factor, designated PE-2/ERF. Finally, we have cloned and characterized the human GATA-1 and GATA-2 genes and promoters and demonstrate that signaling through the Kit signal transduction pathway has direct effects on these genes, showing that Kit signal transduction in setting up the erythroid developmental program.

This laboratory also has isolated the gene encoding the T cell specific gene CD7, expressed in T cell progenitors. We have determined that the promoter has several motifs similar to the Thy-1 gene and lck gene and present in the murine CD7 gene. We have made transgenic mice carrying the human CD7 gene and find that it is expressed in a pattern similar to the murine gene. These studies and other biochemical studies have helped identify a region of the gene that binds a T cell specific transcription factor. This factor is now being characterized.

Key Words:Hematopoiesis, c-kit, ets, erythropoiesis, leukemia, gene regulation

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